Thyroid Hormone
Correct Mechanism
Negative Feedback
Diagram of Negative Feedback Loop
At the end, both TSH and TRH shut down
and the loop starts over again.
TSH (Thyroid Stimulating Hormone) then receives
the signal and stimulates Thyroid Hormones.
TRH (Thyroid Releasing Hormone) stimulates TSH
Produces and Releases
-Triiodothyronine (T3)
-Thyroxine (T4)
Thyroxine (T4)
the inactive form and most of it is converted to an active form called triiodothyronine by organs such as the liver and kidneys.
Triiodothyroine (T3)
affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Produces calcitonin
Regulating Calcium Levels in Animals
helps control blood calcium levels
Regulates metabolism
Faulty/Impaired Mechanism
Too little hormone secretion - hypothyroidism
Cannot keep pituitary gland from secreting TSH -
leads to enlargement of thyroid gland and swelling
of neck (goiter)
Mutations in the receptor beta gene abolish ligand binding
Is a dominant trait
Affected children show attention-deficit disorder
Individuals with this mutation show type of hypothyroidism
characterized by goiter, elevated T3 and thyroxine,
normal/elevated TSH
Too much hormone secretion - hyperthyroidism
Graves' disease - autoimmune disorder - immune system produces antibodies that activate thyroid hormone production
High body temperature, sweating, weight loss,
high blood pressure, irritability
Cell Signaling Pathway
How the Thyroid Hormone Works
Ligand-bound State
Ligand-free State
Receptors:
~trans activation domain
~DNA binding domain
~ligand-binding and dimerization
*BIND TO SEQUENCES OF DNA
(T3 RESPONSE ELEMENTS [TREs]*
Mammalian thyroid hormone receptors consist of:
~alpha-1 gene ~beta-1 gene
~alpha-2 gene ~beta-2 gene
Thyroid Scan
Current Direction of Research
Future work - scientists research effects of long-term
suppression of TSH (thyroid stimulating hormone) on AMD
Possible link between thyroxine and deterioration of eyesight in elderly people (AMD)
excess of thyroid hormones seem to
accelerate deterioration of cones in the retinas
People with hyperthyroidism have highest risk
of AMD
discovered that higher levels of free thyroxine
mean increased risk of AMD
experimented on mice
lacking both alpha isoforms: died within first few weeks
beta-2 disruption: normal hearing, elevated TSH
mild disruption of entire beta gene: deafness,
elevated TSH
no alpha-1 receptor: low body temperature,
mild cardiac malfunctions
Basics
Thyroid function required iodine to synthesize T3
and T4 to send negative feedback to pituitary gland,
which secrets TSH
Vertebrates need thyroid hormones for bone-forming cells
and nerve cells during development
maintain normal blood pressure, heart rate, digestive function
Regulates homeostasis and development
Two very similar hormones from amino acid tyrosine
Thyroid mainly secretes T4 - cells convert most
into T3
Thyroxine (T4) - four iodine atoms
Triiodothyronine (T3) - three iodine atoms
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